Parental Tobacco Smoking and the Risk of Acute Myeloid Leukemia in Children: the Childhood Leukemia International Consortium (CLIC).

n/

Исследование острой токсичности монокатионного производного хлорина е6 – перспективного фотосенсибилизатора для антимикробной и противоопухолевой фотодинамической терапии

In this experimental work the acute toxicity of a chemically modified derivative of the natural pigment chlorophyll a called monocationic chlorin e6, which is a promising photosensitizer (PS) for antimicrobial and antitumor photodynamic therapy, was studied using white rats. The advantages of the PS under investigation are an intense absorption in the long-wavelength region of the visible spectrum, a sufficiently high quantum yield of singlet oxygen generation, pronounced amphiphilic properties along with an appropriate solubility in water, and a high level of photocytotoxic- ity in relation to both malignant HeLa cells and antibiotic-resistant hospital strains of E. сoli bacteria., P. aerugenosa and others. It has been shown that the value of LD50 of the considered PS can be calculated as the value of 100 mg/kg. In the reproduced experimental model of acute toxicity, pathomorphological changes in the vital organs of laboratory animals indicate a pronounced vasopathic effect of the drug with the development of cerebral edema and respiratory distress syndrome, which have become the main signs of thanatogenesis.На белых крысах изучены особенности острой токсичности химически модифицированного производного природного пигмента хлорофилла а монокатионного хлорина e6 – перспективного фотосенсибилизатора (ФС) для антимикробной и противоопухолевой фотодинамической терапии. Преимуществами ФС являются интенсивное поглощение в длинноволновой области видимого спектра, достаточно высокий квантовый выход генерации синглетного кислорода, выраженные амфифильные свойства наряду с хорошей растворимостью в воде и высокий уровень фотоцитотоксичности в отношении как злокачественных клеток линии HeLa, так и антибиотикорезистентных госпитальных штаммов бактерий E. coli, P. Aerugenosa и других. Величина ЛД50 для монокатионного хлорина e6 составляет 100 мг/кг массы тела. В воспроизведенной экспериментальной модели острой токсичности патоморфологические изменения жизненно важных органов лабораторных животных свидетельствуют о выраженном вазопатическом действии препарата с развитием отека головного мозга и респираторного дистресс-синдрома, ставшими основными звеньями танатогенеза

Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium

Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol

Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium (INHANCE)

Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol. We carried out a pooled analysis of 8981 cases of head and neck cancer and 10090 controls from 12 case-control studies with comparable information on mouthwash use in the International Head and Neck Cancer Epidemiology Consortium. Logistic regression was used to assess the association of mouthwash use with cancers of the oral cavity, oropharynx, hypopharynx, and larynx, adjusting for study, age, sex, pack-years of tobacco smoking, number of alcoholic drinks/day, and education. Compared with never users of mouthwash, the odds ratio (OR) of all head and neck cancers was 1.01 [95% confidence interval (CI): 0.94-1.08] for ever users, based on 12 studies. The corresponding ORs of cancer of the oral cavity and oropharynx were 1.11 (95% CI: 1.00-1.23) and 1.28 (95% CI: 1.06-1.56), respectively. OR for all head and neck cancer was 1.15 (95% CI: 1.01-1.30) for use for more than 35 years, based on seven studies (P for linear trend=0.01), and OR 1.31 (95% CI: 1.09-1.58) for use more than one per day, based on five studies (P for linear trend <0.001). Although limited by the retrospective nature of the study and the limited ability to assess risks of mouthwash use in nonusers of tobacco and alcohol, this large investigation shows potential risks for head and neck cancer subsites and in long-term and frequent users of mouthwash. This pooled analysis provides the most precise estimate of the association between mouthwash use and head and neck cancer

Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10244 head and neck cancer case subjects and 15227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiolog

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Background Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) ≤18.5 kg/m2 (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m2 (0.52, 0.44-0.60) and BMI ≥30 kg/m2 (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI ≤18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studie

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

Background Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. Methods We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Results Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after ≥20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after ≥20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. Conclusions Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cance

A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer

© The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] Funding This work was supported the National Institutes of Health (R01CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). Notes The authors thank all of the participants who took part in this research and the funders and technical staff who made this study possible. We acknowledge and thank Simone Benhamou (INSERM, France) for sample contributions. We also acknowledge and thank The Cancer Genome Atlas initiative, whose data contributed heavily to this study.Peer reviewedPublisher PD

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

Acknowledgments: The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. We also acknowledge and thank The Cancer Genome Atlas initiative whose data contributed heavily to this study. Funding: Funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD